Center Volume Impacts Readmissions and Mortality after Congenital Cardiac Surgery.

OBJECTIVE: To characterize the relationship between surgical volume and postoperative outcomes in congenital heart surgery, we used a national cohort to assess the costs, readmissions, and complications in children undergoing cardiac operations. STUDY DESIGN: The Nationwide Readmissions Database was used to identify pediatric patients (≤18 years) undergoing congenital cardiac surgery from 2010 to 2017. Hospitals were categorized based on deciles and tertiles of annual caseload with high-volume categorized as the highest tertile of volume. Multivariable regression models adjusting for patient and hospital characteristics were used to study the impact of volume on 30-day nonelective readmission, mortality, home discharge, and resource use. RESULTS: Of an estimated 69 448 hospitalizations included for analysis, 56 672 (82%) occurred at high-volume centers. After adjustment for key clinical factors, each decile increase in volume was associated with a 25% relative decrease in the odds of mortality, a 14% decrease in the odds of nonhome discharge, and a 4% relative decrease in the likelihood of 30-day nonelective readmission. After risk adjustment, each incremental increase in volume decile was associated with a one-half-day decrease in the hospital length of stay, but did not alter costs of the index hospitalization. However, after including all readmissions within 30 days of the index discharge, high-volume centers were associated with significantly lower costs compared with low-volume hospitals. CONCLUSIONS: Increased congenital cardiac surgery volume is associated with improved mortality, reduced duration of hospitalization, 30-day readmissions, and resource use. These findings demonstrate the inverse relationship between hospital volume and resource use and may have implications for the centralization of care for congenital cardiac surgery.

Machine Learning in Drug Discovery and Development Part 1: A Primer.

Artificial intelligence, in particular machine learning (ML), has emerged as a key promising pillar to overcome the high failure rate in drug development. Here, we present a primer on the ML algorithms most commonly used in drug discovery and development. We also list possible data sources, describe good practices for ML model development and validation, and share a reproducible example. A companion article will summarize applications of ML in drug discovery, drug development, and postapproval phase.

Delayed delivery of endothelial progenitor cell-derived extracellular vesicles via shear thinning gel improves postinfarct hemodynamics.

BACKGROUND: Extracellular vesicles (EVs) are promising therapeutics for cardiovascular disease, but poorly-timed delivery might hinder efficacy. We characterized the time-dependent response to endothelial progenitor cell (EPC)-EVs within an injectable shear-thinning hydrogel (STG+EV) post-myocardial infarction (MI) to identify when an optimal response is achieved. METHODS: The angiogenic effects of prolonged hypoxia on cell response to EPC-EV therapy and EV uptake affinity were tested in vitro. A rat model of acute MI via left anterior descending artery ligation was created and STG+EV was delivered via intramyocardial injections into the infarct border zone at time points corresponding to phases of post-MI inflammation: 0 hours (immediate), 3 hours (acute inflammation), 4 days (proliferative), and 2 weeks (fibrosis). Hemodynamics 4 weeks post-treatment were compared across treatment and control groups (phosphate buffered saline [PBS], shear-thinning gel). Scar thickness and ventricular diameter were assessed histologically. The primary hemodynamic end point was end systolic elastance. The secondary end point was scar thickness. RESULTS: EPC-EVs incubated with chronically versus acutely hypoxic human umbilical vein endothelial cells resulted in a 2.56 ± 0.53 versus 1.65 ± 0.15-fold increase (P = .05) in a number of vascular meshes and higher uptake of EVs over 14 hours. End systolic elastance improved with STG+EV therapy at 4 days (0.54 ± 0.08) versus PBS or shear-thinning gel (0.26 ± 0.03 [P = .02]; 0.23 ± 0.02 [P = .01]). Preservation of ventricular diameter (6.20 ± 0.73 mm vs 8.58 ± 0.38 mm [P = .04]; 9.13 ± 0.25 mm [P = .01]) and scar thickness (0.89 ± 0.05 mm vs 0.62 ± 0.03 mm [P < .0001] and 0.58 ± 0.05 mm [P < .0001]) was significantly greater at 4 days, compared wit PBS and shear-thinning gel controls. CONCLUSIONS: Delivery of STG+EV 4 days post-MI improved left ventricular contractility and preserved global ventricular geometry, compared with controls and immediate therapy post-MI. These findings suggest other cell-derived therapies can be optimized by strategic timing of therapeutic intervention.

Urolithiasis associated with topiramate

OBJECTIVE: Topiramate is a sulfamate-substituted monosaccharide anticonvulsant used as adjunctive therapy for intractable refractory seizures. It is report a case of topiramate-induced urolithiasis. CASE REPORT: A 35-year-old man presented with acute, right-sided, colicky flank pain. He denied hematuria or dysuria. He was in use of phenytoin, risperidone, phenobarbital, and topiramate. The total daily dose of topiramate was 375 mg. A CT scan showed a 7 x 1 mm curvilinear density at the right ureterovesical junction with proximal hydrouretronephrosis. He was managed with rigid ureteroscopic stone extraction and the calculus metabolic analysis revealed the stone was composed of carbonate apatite (70 percent), calcium oxalate dihydrate (20 percent), and calcium oxalate monohydrate (10 percent). COMMENTS: The present case typifies many features of topiramate-induced urolithiasis. Those who care for patients with urinary stone disease should be aware of this association.

Urolithiasis associated with topiramate.

OBJECTIVE: Topiramate is a sulfamate-substituted monosaccharide anticonvulsant used as adjunctive therapy for intractable refractory seizures. It is report a case of topiramate-induced urolithiasis. CASE REPORT: A 35-year-old man presented with acute, right-sided, colicky flank pain. He denied hematuria or dysuria. He was in use of phenytoin, risperidone, phenobarbital, and topiramate. The total daily dose of topiramate was 375 mg. A CT scan showed a 7 x 1 mm curvilinear density at the right ureterovesical junction with proximal hydrouretronephrosis. He was managed with rigid ureteroscopic stone extraction and the calculus metabolic analysis revealed the stone was composed of carbonate apatite (70%), calcium oxalate dihydrate (20%), and calcium oxalate monohydrate (10%). COMMENTS: The present case typifies many features of topiramate-induced urolithiasis. Those who care for patients with urinary stone disease should be aware of this association.